Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors

An anti-Hebbian form of LTP is observed at excitatory synapses made with some hippocampal interneurons. LTP induction is facilitated when postsynaptic interneurons are hyperpolarized, presumably because Ca(2+) entry through Ca(2+)-permeable glutamate receptors is enhanced. The contribution of modulatory transmitters to anti-Hebbian LTP induction remains to be established. Activation of group I metabotropic receptors (mGluRs) is required for anti-Hebbian LTP induction in interneurons with cell bodies in the CA1 stratum oriens. This region receives a strong cholinergic innervation from the septum, and muscarinic acetylcholine receptors (mAChRs) share some signaling pathways and cooperate with mGluRs in the control of neuronal excitability.We therefore examined possible interactions between group I mGluRs and mAChRs in anti-Hebbian LTP at synapses which excite oriens interneurons in rat brain slices. We found that blockade of either group I mGluRs or M1 mAChRs prevented the induction of anti-Hebbian LTP by pairing presynaptic activity with postsynaptic hyperpolarization. Blocking either receptor also suppressed long-term effects of activation of the other G-protein coupled receptor on interneuron membrane potential. However, no crossed blockade was detected for mGluR or mAchR effects on interneuron after-burst potentials or on the frequency of miniature EPSPs. Paired recordings between pyramidal neurons and oriens interneurons were obtained to determine whether LTP could be induced without concurrent stimulation of cholinergic axons. Exogenous activation of mAChRs led to LTP, with changes in EPSP amplitude distributions consistent with a presynaptic locus of expression. LTP, however, required noninvasive presynaptic and postsynaptic recordings

Selective Metal Cation Capture by Soft Anionic Metal-Organic Frameworks via Drastic Single-Crystal-to-Single-Crystal Transformations

In this paper we describe a novel framework for the discovery of the topical content of a data corpus, and the tracking of its complex structural changes across the temporal dimension. In contrast to previous work our model does not impose a prior on the rate at which documents are added to the corpus nor does it adopt the Markovian assumption which overly restricts the type of changes that the model can capture. Our key technical contribution is a framework based on (i) discretization of time into epochs, (ii) epoch-wise topic discovery using a hierarchical Dirichlet process-based model, and (iii) a temporal similarity graph which allows for the modelling of complex topic changes: emergence and disappearance, evolution, and splitting and merging. The power of the proposed framework is demonstrated on the medical literature corpus concerned with the autism spectrum disorder (ASD) - an increasingly important research subject of significant social and healthcare importance. In addition to the collected ASD literature corpus which we will make freely available, our contributions also include two free online tools we built as aids to ASD researchers. These can be used for semantically meaningful navigation and searching, as well as knowledge discovery from this large and rapidly growing corpus of literature.Comment: In Proc. Pacific-Asia Conference on Knowledge Discovery and Data Mining (PAKDD), 201

Cross-sectional evaluation of a longitudinal consultation skills course at a new UK medical school

Background: Good communication is a crucial element of good clinical care, and it is important to provide appropriate consultation skills teaching in undergraduate medical training to ensure that doctors have the necessary skills to communicate effectively with patients and other key stakeholders. This article aims to provide research evidence of the acceptability of a longitudinal consultation skills strand in an undergraduate medical course, as assessed by a cross-sectional evaluation of students' perceptions of their teaching and learning experiences. Methods: A structured questionnaire was used to collect student views. The questionnaire comprised two parts: 16 closed questions to evaluate content and process of teaching and 5 open-ended questions. Questionnaires were completed at the end of each consultation skills session across all year groups during the 2006-7 academic year (5 sessions in Year 1, 3 in Year 2, 3 in Year 3, 10 in Year 4 and 10 in Year 5). 2519 questionnaires were returned in total. Results: Students rated Tutor Facilitation most favourably, followed by Teaching, then Practice & Feedback, with suitability of the Rooms being most poorly rated. All years listed the following as important aspects they had learnt during the session: • how to structure the consultation • importance of patient-centredness • aspects of professionalism (including recognising own limits, being prepared, generally acting professionally). All years also noted that the sessions had increased their confidence, particularly through practice. Conclusions: Our results suggest that a longitudinal and integrated approach to teaching consultation skills using a well structured model such as Calgary-Cambridge, facilitates and consolidates learning of desired process skills, increases student confidence, encourages integration of process and content, and reinforces appreciation of patient-centredness and professionalism

Diagnosing the Role of Alfvén Waves in Magnetosphere-Ionosphere Coupling: Swarm Observations of Large Amplitude Nonstationary Magnetic Perturbations During an Interval of Northward IMF

High-resolution multispacecraft Swarm data are used to examine magnetosphere-ionosphere coupling during a period of northward interplanetary magnetic field (IMF) on 31 May 2014. The observations reveal a prevalence of unexpectedly large amplitude (>100 nT) and time-varying magnetic perturbations during the polar passes, with especially large amplitude magnetic perturbations being associated with large-scale downward field-aligned currents. Differences between the magnetic field measurements sampled at 50 Hz from Swarm A and C, approximately 10 s apart along track, and the correspondence between the observed electric and magnetic fields at 16 samples per second, provide significant evidence for an important role for Alfvén waves in magnetosphere-ionosphere coupling even during northward IMF conditions. Spectral comparison between the wave E- and B-fields reveals a frequency-dependent phase difference and amplitude ratio consistent with interference between incident and reflected Alfvén waves. At low frequencies, the E/B ratio is in phase with an amplitude determined by the Pedersen conductance. At higher frequencies, the amplitude and phase change as a function of frequency in good agreement with an ionospheric Alfvén resonator model including Pedersen conductance effects. Indeed, within this Alfvén wave incidence, reflection, and interference paradigm, even quasi-static field-aligned currents might be reasonably interpreted as very low frequency (ω → 0) Alfvén waves. Overall, our results not only indicate the importance of Alfvén waves for magnetosphere-ionosphere coupling but also demonstrate a method for using Swarm data for the innovative experimental diagnosis of Pedersen conductance from low-Earth orbit satellite measurements

Reporting accuracy of packed lunch consumption among Danish 11-year-olds differ by gender.

Background: Packed lunch is the dominant lunch format in many countries including Denmark. School lunch is consumed unsupervised, and self-reported recalls are appropriate in the school setting. However, little is known about the accuracy of recalls in relation to packed lunch. Objective: To assess the qualitative recall accuracy of self-reported consumption of packed lunch among Danish 11-year-old children in relation to gender and dietary assessment method. Design: A cross-sectional dietary recall study of packed lunch consumption. Digital images (DIs) served as an objective reference method to determine food items consumed. Recalls were collected with a lunch recall questionnaire (LRQ) comprising an open-ended recall (OE-Q) and a pre-coded food group prompted recall (PC-Q). Individual interviews (INTs) were conducted successively. The number of food items was identified and accuracy was calculated as match rates (% identified by DIs and reported correctly) and intrusion rates (% not identified by DIs but reported) were determined. Setting and subjects: Three Danish public schools from Copenhagen. A total of 114 Danish 11-year-old children, mean (SE) age=11.1 (0.03), and body mass index=18.2 (0.26). Results: The reference (DIs) showed that girls consumed a higher number of food items than boys [mean (SE) 5.4 (0.25) vs. 4.6 (0.29) items (p=0.05)]. The number of food items recalled differed between genders with OE-Q recalls (p=0.005) only. Girls’ interview recalls were more accurate than boys’ with higher match rates (p=0.04) and lower intrusion rates (p=0.05). Match rates ranged from 67–90% and intrusion rates ranged from 13–39% with little differences between girls and boys using the OE-Q and PC-Q methods. Conclusion: Dietary recall validation studies should not only consider match rates as an account of accuracy. Intrusions contribute to over-reporting in non-validation studies, and future studies should address recall accuracy and inaccuracies in relation to gender and recall method

Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)

New Canadian natural health product regulations: a qualitative study of how CAM practitioners perceive they will be impacted

BACKGROUND: New Canadian policy to regulate natural health products (NHPs), such as herbs and vitamins were implemented on January 1(st), 2004. We explored complementary and alternative medicine (CAM) practitioners' perceptions of how the new regulations may affect their practices and relationships with patients/consumers. METHODS: This was an applied ethnographic study. Data were collected in fall 2004 via qualitative interviews with 37 Canadian leaders of four CAM groups that use natural products as a core part of their practises: naturopathic medicine, traditional Chinese medicine (TCM), homeopathic medicine and Western herbalism. All interviews were transcribed verbatim and coded independently by a minimum of two investigators using content analysis. RESULTS: Three key findings emerged from the data: 1) all CAM leaders were concerned with issues of their own access to NHPs; 2) all the CAM leaders, except for the homeopathic leaders, specifically indicated a desire to have a restricted schedule of NHPs; and 3) only naturopathic leaders were concerned the NHP regulations could potentially endanger patients if they self-medicate incorrectly. CONCLUSION: Naturopaths, TCM practitioners, homeopaths, and Western herbalists were all concerned about how the new NHP regulations will affect their access to the products they need to practice effectively. Additional research will need to focus on what impacts actually occur as the regulations are implemented more fully

MagneToRE: Mapping the 3-D Magnetic Structure of the Solar Wind Using a Large Constellation of Nanosatellites

Unlike the vast majority of astrophysical plasmas, the solar wind is accessible to spacecraft, which for decades have carried in-situ instruments for directly measuring its particles and fields. Though such measurements provide precise and detailed information, a single spacecraft on its own cannot disentangle spatial and temporal fluctuations. Even a modest constellation of in-situ spacecraft, though capable of characterizing fluctuations at one or more scales, cannot fully determine the plasma’s 3-D structure. We describe here a concept for a new mission, the Magnetic Topology Reconstruction Explorer (MagneToRE), that would comprise a large constellation of in-situ spacecraft and would, for the first time, enable 3-D maps to be reconstructed of the solar wind’s dynamic magnetic structure. Each of these nanosatellites would be based on the CubeSat form-factor and carry a compact fluxgate magnetometer. A larger spacecraft would deploy these smaller ones and also serve as their telemetry link to the ground and as a host for ancillary scientific instruments. Such an ambitious mission would be feasible under typical funding constraints thanks to advances in the miniaturization of spacecraft and instruments and breakthroughs in data science and machine learning

Multi-decadal trends in large-bodied fish populations in the New South Wales Murray-Darling Basin, Australia

Context: Native fish populations in Australia's Murray-Darling Basin (MDB) have experienced severe declines since European settlement. Information on their status is needed to guide management and recovery. Aims: To quantify trends in MDB fish populations in New South Wales (NSW) from 1994 to 2022. Methods: Relative abundance, biomass, and size structure were examined using generalised additive mixed models at NSW MDB and river catchment (valley) scales for five native species (Murray cod, Maccullochella peelii, golden perch, Macquaria ambigua, silver perch, Bidyanus bidyanus, Macquarie perch, Macquaria australasica, freshwater catfish, Tandanus tandanus) and one alien species (common carp, Cyprinus carpio). Key results: There was strong inter-annual variation in relative abundance, biomass and population structure for all species. At the Basin scale, relative abundance of Murray cod, golden perch and common carp increased across the time series, with no clear trends for silver perch, Macquarie perch or freshwater catfish. Patterns in relative abundance, biomass, and population structure were variable among valleys for most species. Conclusions and implications: Although native fish populations in the MDB remain degraded and face escalating threats, recent increases in the abundance of some native species are an encouraging sign that integrated restoration efforts can improve the outlook for native fish

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1